WO2000074774A1 - Ionophoretic drug delivery device - Google Patents

Ionophoretic drug delivery device Download PDF

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Publication number
WO2000074774A1
WO2000074774A1 PCT/IT2000/000227 IT0000227W WO0074774A1 WO 2000074774 A1 WO2000074774 A1 WO 2000074774A1 IT 0000227 W IT0000227 W IT 0000227W WO 0074774 A1 WO0074774 A1 WO 0074774A1
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WO
WIPO (PCT)
Prior art keywords
waveform
current
electrodes
active compound
modulator
Prior art date
Application number
PCT/IT2000/000227
Other languages
French (fr)
Inventor
Antonino D'africa
Guido Paduano
Massimo Sartori
Original Assignee
Africa Antonino D
Guido Paduano
Massimo Sartori
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=11353020&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2000074774(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Africa Antonino D, Guido Paduano, Massimo Sartori filed Critical Africa Antonino D
Priority to KR1020017015852A priority Critical patent/KR20020006547A/en
Priority to DK00940738T priority patent/DK1185334T3/en
Priority to AT00940738T priority patent/ATE279957T1/en
Priority to EP00940738A priority patent/EP1185334B1/en
Priority to JP2001501305A priority patent/JP2003501166A/en
Priority to CA002376251A priority patent/CA2376251A1/en
Priority to BR0011459-6A priority patent/BR0011459A/en
Priority to AU55636/00A priority patent/AU773339B2/en
Priority to DE60015125T priority patent/DE60015125T2/en
Publication of WO2000074774A1 publication Critical patent/WO2000074774A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
    • A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0432—Anode and cathode
    • A61N1/044—Shape of the electrode
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0448—Drug reservoir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/325—Applying electric currents by contact electrodes alternating or intermittent currents for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0432—Anode and cathode
    • A61N1/0436—Material of the electrode

Definitions

  • This invention relates to a device and method for the transdermal administration of active compounds by hydroelectrophoresis and ionophoresis.
  • active compounds of various kinds can be administered by ionophoresis, by applying two electrodes to the patient, one of which is fitted with means for holding a solution containing the active compound being administered, while the other electrode comprises a metal plate.
  • the two electrodes are connected electrically to a current generator, normally of the single direction pulsed type. Ions are generated and pass through the barrier represented by the epidermis and enter the underlying tissues, where they are absorbed by the body.
  • Active compounds of various kinds having a therapeutic effect and even a cosmetic effect are administered using this technique.
  • ionophoresis is used for the administration of calcium chloride and magnesium chloride solutions as an analgesic, hydrocortisones and other anti-inflammatories and other products.
  • the currents used in these administration techniques may be of various forms.
  • one-way pulsed or sinusoidal currents which may be frequency-modulated, amplitude-modulated and in some cases both frequency-modulated and amplitude-modulated are used.
  • the ionophoretic method has some defects however, the main one being the poor efficiency of transdermal transport and distribution of the active compound almost exclusively in the surface areas of tissue.
  • cryoeiectrophoresis a frozen solution of active compound which however has the disadvantage of appreciable surface dispersion of the drug during treatment as a result of the Joule effect, with the result that a maximum of only 5% of the active compound can be transported. It is also true that cryoeiectrophoresis does not introduce the drug into the systemic circulation, but this is exclusively due to vasoconstriction at the points of contact between the frozen solution and the skin, and the fact that in the physical condition of the solution (solid) electrophoretic mobility is zero.
  • a device for the transdermal administration of an active compound comprising electrodes which are to be applied to a patient, one of which is capable of holding a vehicle containing the active compound, characterized in that the generator generates a one-way amplitude-modulated current between said electrodes by means of a modulator having a periodical function.
  • one-way current is genericaliy meant any current having a constant sign, and therefore capable of generating an ionophoretic effect, which varies periodically between a minimum value and a maximum value.
  • the maximum value, and therefore the maximum amplitude of the current voltage between the electrodes, is modulated by means of a periodical modulating signal, e.g. a triangular waveform.
  • the modulating signal may have a variable course between a minimum value and a maximum value, where the minimum value is preferably equal to zero.
  • the one-way current may have a waveform selected from the group comprising: a positive sinusoidal waveform, a rectified sinusoidal waveform, a half-sinusoidal waveform, a triangular or sawtooth waveform, a square waveform or equivalent waveforms periodically oscillating between zero and a maximum amplitude value modulated as above.
  • the modulating signal may have a waveform selected from the group comprising: a triangular waveform, a rectified sinusoidal waveform, a half- sinusoidal waveform, a trapezoidal waveform, or combinations thereof.
  • the invention also relates to a method for the administration of an active compound via the transdermal route comprising the stages of:
  • Figure 1 shows a diagram of the equipment for transdermal molecular transport
  • Figure 2 shows the waveform of the carrier signal
  • Figure 3 shows the waveform of the modulating signal
  • Figure 4 shows the modulated waveform for the current generated by the device
  • Figures 5 to 9 show other possible waveforms for the carrier signal
  • Figures 10 to 12 show other alternative forms of the modulating signal
  • Figure 13 shows a modulated waveform with a triangular modulator
  • Figure 14 shows diagrams of experimental data.
  • FIG 1 shows, extremely diagrammatically, equipment for transdermal molecular transport generically indicated by 1 to which are attached two electrodes 3 and 5, connected to equipment 1 by means of wires 7 and 9.
  • Electrode 5 is generically a flexible metal sheet which can be applied so that it fits the anatomical shape of the area of the patient's body to which the electrode has to be applied, and this will normally be a negative electrode.
  • Electrode 3 is constructed in such a way as to contain an active compound which has to be administered by transdermal means.
  • the active compound is normally held in a liquid or frozen solution, in a gel or in other means.
  • the method by which the active compound is held on electrode 3 and released by it is not restrictive, and likewise the nature of the active compound, which may be a drug, for example an analgesic or anaesthetic, a product for the treatment of skin blemishes, cellulitis or the like, is not restrictive.
  • active compounds suspended in gels e.g. agarose.
  • the current generated between electrodes 3 and 5 has a special waveform comprising an amplitude- modulated signal obtained from the modulation of a carrier signal comprising e.g. a rectified sinusoidal wave or the like.
  • Figure 2 represents by way of example a first waveform for which the carrier signal comprises a rectified sinusoidal wave. This signal has a frequency typically between 100 and 3000 Hz. A greater depth of penetration by the ions or molecules of the active compound conveyed through the electric field generated between two electrodes 3 and 5 is obtained at lower frequencies.
  • the carrier signal illustrated in Figure 2 is modulated e.g. by means of a sawtooth modulating signal of the type shown in Figure 3.
  • the frequency of the modulating signal may lie e.g. between 0J and 5 Hz and preferably between 0.5 and 1 Hz.
  • Figure 4 shows the current waveform and the voltage between the electrodes applied to the patient obtained with the modulator in Figure 3 applied to the carrier in Figure 2.
  • the currents used have a maximum strength of approximately 100 mA.
  • Figures 5 to 9 show examples of carrier signals constituted in the order of: a positive sinusoidal waveform, a triangular waveform, a positive square waveform, a sawtooth waveform, a series of spaced pulses.
  • carrier signals can be modulated with a modulator having the sawtooth waveform in Figure 3, and also by different modulators, e.g. of triangular shape as in Figure 10 or rectified sinusoidal as in Figure 11 or trapezoidal as in Figure 12.
  • Figure 13 shows the waveform which can be obtained from modulating the signal in Figure 2 by the modulator in Figure 10.
  • the waveforms are merely indicative, in particular the ratios between the frequency of the base signal and the modulator are not respected.
  • Determinations level with the skin, 3 cm from the skin and 6 cm from the skin were performed in all the groups.
  • the tissues were homogenized and dissolved in 2.5 ml of 1 N NaOH and the radioactivity of the solutions was measured.
  • Administration was performed using currents at 500, 1000 and 2000 Hz.
  • the radioactivity measurements indicate that cryoeiectrophoresis is wholly ineffective for transdermal transport of the labelled compound used.
  • Hydroelectrophoresis using an agarose gel improved migration of the radioactive compound while the electrical field was active, and the use of the waveform according to the invention created an ideal ionic force for favouring the transdermal passage of labelled progesterone.
  • hydroelectrophoresis performed using the waveform according to this invention is an effectively innovative procedure in the transdermal transport of drugs, whether or not they can be ionized.

Abstract

The device (1) for the transdermal administration of an active compound comprises a current generator and at least one pair of electrode (3, 5) for application to a patient, one of which is designed to contain a vehicle containing the active compound. The generator generates a one-way amplitude-modulated current between said electrodes through a modulator having a periodical function.

Description

IONOPHORETIC DRUG DELIVERY DEVICE
DESCRIPTION This invention relates to a device and method for the transdermal administration of active compounds by hydroelectrophoresis and ionophoresis.
It is known that active compounds of various kinds can be administered by ionophoresis, by applying two electrodes to the patient, one of which is fitted with means for holding a solution containing the active compound being administered, while the other electrode comprises a metal plate. The two electrodes are connected electrically to a current generator, normally of the single direction pulsed type. Ions are generated and pass through the barrier represented by the epidermis and enter the underlying tissues, where they are absorbed by the body.
Active compounds of various kinds having a therapeutic effect and even a cosmetic effect are administered using this technique. For example, in the more strictly therapeutic sector, ionophoresis is used for the administration of calcium chloride and magnesium chloride solutions as an analgesic, hydrocortisones and other anti-inflammatories and other products.
Devices and electrodes of a special shape for the transdermal administration of active compounds are described in EP-A-0292930, US-A- 5,084,008, WO-A-8808729, WO-A-9622810.
The currents used in these administration techniques may be of various forms. In general one-way pulsed or sinusoidal currents which may be frequency-modulated, amplitude-modulated and in some cases both frequency-modulated and amplitude-modulated are used.
The ionophoretic method has some defects however, the main one being the poor efficiency of transdermal transport and distribution of the active compound almost exclusively in the surface areas of tissue.
A technical improvement in ionophoresis has recently been suggested which uses a frozen solution of active compound (cryoeiectrophoresis) which however has the disadvantage of appreciable surface dispersion of the drug during treatment as a result of the Joule effect, with the result that a maximum of only 5% of the active compound can be transported. It is also true that cryoeiectrophoresis does not introduce the drug into the systemic circulation, but this is exclusively due to vasoconstriction at the points of contact between the frozen solution and the skin, and the fact that in the physical condition of the solution (solid) electrophoretic mobility is zero.
Surprisingly it has now been found, and this constitutes the subject matter of this invention, that a particular conformation of the current waveform and the voltage between the electrodes favours the administration of active compounds via the transdermal route in comparison with the waveforms conventionally used.
In substance, in accordance with the invention a device is provided for the transdermal administration of an active compound comprising electrodes which are to be applied to a patient, one of which is capable of holding a vehicle containing the active compound, characterized in that the generator generates a one-way amplitude-modulated current between said electrodes by means of a modulator having a periodical function.
By one-way current is genericaliy meant any current having a constant sign, and therefore capable of generating an ionophoretic effect, which varies periodically between a minimum value and a maximum value. The maximum value, and therefore the maximum amplitude of the current voltage between the electrodes, is modulated by means of a periodical modulating signal, e.g. a triangular waveform.
The modulating signal may have a variable course between a minimum value and a maximum value, where the minimum value is preferably equal to zero.
The one-way current may have a waveform selected from the group comprising: a positive sinusoidal waveform, a rectified sinusoidal waveform, a half-sinusoidal waveform, a triangular or sawtooth waveform, a square waveform or equivalent waveforms periodically oscillating between zero and a maximum amplitude value modulated as above.
The modulating signal may have a waveform selected from the group comprising: a triangular waveform, a rectified sinusoidal waveform, a half- sinusoidal waveform, a trapezoidal waveform, or combinations thereof.
The invention also relates to a method for the administration of an active compound via the transdermal route comprising the stages of:
• applying two electrodes, one of which is associated with a vehicle containing the active compound,
• generating a one-way current which is amplitude-modulated by a modulating signal of a periodical nature between said two electrodes.
Further advantageous features of the device and the method according to the invention are indicated in the dependent claims and in the following description of some embodiments.
The invention will be better understood from the description and the appended drawing, which illustrates non-restrictive embodiments of the invention. The various figures and in particular the waveform diagrams are indicative and not to scale. In the drawing: Figure 1 shows a diagram of the equipment for transdermal molecular transport,
Figure 2 shows the waveform of the carrier signal, Figure 3 shows the waveform of the modulating signal, Figure 4 shows the modulated waveform for the current generated by the device,
Figures 5 to 9 show other possible waveforms for the carrier signal, Figures 10 to 12 show other alternative forms of the modulating signal, Figure 13 shows a modulated waveform with a triangular modulator, and Figure 14 shows diagrams of experimental data.
Figure 1 shows, extremely diagrammatically, equipment for transdermal molecular transport generically indicated by 1 to which are attached two electrodes 3 and 5, connected to equipment 1 by means of wires 7 and 9.
Electrode 5 is generically a flexible metal sheet which can be applied so that it fits the anatomical shape of the area of the patient's body to which the electrode has to be applied, and this will normally be a negative electrode.
Electrode 3, generally positive, is constructed in such a way as to contain an active compound which has to be administered by transdermal means. The active compound is normally held in a liquid or frozen solution, in a gel or in other means. For the purposes of this invention the method by which the active compound is held on electrode 3 and released by it is not restrictive, and likewise the nature of the active compound, which may be a drug, for example an analgesic or anaesthetic, a product for the treatment of skin blemishes, cellulitis or the like, is not restrictive. However, optimum results are obtained with active compounds suspended in gels, e.g. agarose.
The conformation of the electrodes and the generator are known to those skilled in the art and will not be described in greater detail here.
In accordance with the invention the current generated between electrodes 3 and 5 has a special waveform comprising an amplitude- modulated signal obtained from the modulation of a carrier signal comprising e.g. a rectified sinusoidal wave or the like. Figure 2 represents by way of example a first waveform for which the carrier signal comprises a rectified sinusoidal wave. This signal has a frequency typically between 100 and 3000 Hz. A greater depth of penetration by the ions or molecules of the active compound conveyed through the electric field generated between two electrodes 3 and 5 is obtained at lower frequencies. The carrier signal illustrated in Figure 2 is modulated e.g. by means of a sawtooth modulating signal of the type shown in Figure 3. The frequency of the modulating signal may lie e.g. between 0J and 5 Hz and preferably between 0.5 and 1 Hz.
Figure 4 shows the current waveform and the voltage between the electrodes applied to the patient obtained with the modulator in Figure 3 applied to the carrier in Figure 2. Typically the currents used have a maximum strength of approximately 100 mA.
The application of an oscillating voltage having an amplitude which is modulated in a periodic way as illustrated in Figure 4 results in improved transdermal transfer capacity for the active compounds. Similar results can be obtained by using various waveforms for the carrier signal and various waveforms for the modulating signal, provided that the basic principle represented by the fact that the carrier signal is amplitude-modulated by a modulating signal of a periodic form which varies between zero and a maximum value is maintained.
Figures 5 to 9 show examples of carrier signals constituted in the order of: a positive sinusoidal waveform, a triangular waveform, a positive square waveform, a sawtooth waveform, a series of spaced pulses.
These carrier signals can be modulated with a modulator having the sawtooth waveform in Figure 3, and also by different modulators, e.g. of triangular shape as in Figure 10 or rectified sinusoidal as in Figure 11 or trapezoidal as in Figure 12.
Figure 13 shows the waveform which can be obtained from modulating the signal in Figure 2 by the modulator in Figure 10.
In this figure, as in the preceding figures, the waveforms are merely indicative, in particular the ratios between the frequency of the base signal and the modulator are not respected.
The efficiency of the waveform according to the invention in comparison with conventional cryoeiectrophoresis techniques was tested using the following method.
Progesterone solutions labelled with 1 J25 cpm (Byk) 3800 cpm were used. Radioactivity was measured using the SR 300 Tratec (Byk) automatic instrument.
Treatment was applied to adult rabbits of the New Zealand variety having a mean weight of 1.980 kg which had been shaved in the pubic and thoracic areas. Urine samples were obtained using an echography syringe. Blood samples were obtained from the auricular vein.
18 rabbits subdivided into four groups were used, and of these the first three, each consisting of 4 rabbits, were treated by hydroelectrophoresis using labelled progesterone, the third group comprising 3 subgroups of 2 rabbits by cryoeiectrophoresis using labelled progesterone.
Determinations level with the skin, 3 cm from the skin and 6 cm from the skin were performed in all the groups. The tissues were homogenized and dissolved in 2.5 ml of 1 N NaOH and the radioactivity of the solutions was measured. Administration was performed using currents at 500, 1000 and 2000 Hz.
The results are shown in Figure 13. After treatment by cryoeiectrophoresis in the pubic area at 1000 Hz the radioactivity found in urine was 5% of the total, while with hydroelectrophoresis the measured radioactivity was 79.6%. Activity measured in the lungs 6 cm from the skin and at a frequency of 500 Hz was 74.7% for ionophoresis and only 2% for cryoeiectrophoresis. CONCLUSIONS
The radioactivity measurements indicate that cryoeiectrophoresis is wholly ineffective for transdermal transport of the labelled compound used.
This result is explained by the zero electrophoretic mobility of substances in the solid state and the small amount of radioactivity measured in the tissues is due to melting of the solid in contact with the skin and subsequent passage due to ionophoresis.
Hydroelectrophoresis using an agarose gel improved migration of the radioactive compound while the electrical field was active, and the use of the waveform according to the invention created an ideal ionic force for favouring the transdermal passage of labelled progesterone.
It can be concluded that hydroelectrophoresis performed using the waveform according to this invention is an effectively innovative procedure in the transdermal transport of drugs, whether or not they can be ionized.
In the case of non-ionizable molecules penetration is obtained as a result of the polarizability of the molecules. The polarized molecules migrate through the skin, and in particular through the pores, under the effect of the applied electric field.
It is to be understood that the drawing only shows one embodiment merely provided as a practical demonstration of the invention, and said invention may vary in form and arrangement without however going beyond the scope of the concept underlying the invention itself. Any reference numbers present in the attached claims are designed to assist reading of the claims with reference to the description and the drawing, and do not restrict the scope of the protection covered by the claims.

Claims

1. Device for the transdermal administration of an active compound, comprising a current generator and at least one pair of electrodes for application to a patient, one of which must be suitable for holding a vehicle containing the active compound, characterized in that said generator generates a one-way current between said electrodes which is modulated in amplitude by a modulator of a periodic nature.
2. Device according to Claim 1 , characterized in that said modulator has an amplitude which can vary between zero and a maximum value.
3. Device according to Claim 1 or 2, characterized in that the oneway current has a positive sinusoidal waveform.
4. Device according to Claim 1 or 2, characterized in that the oneway current has a rectified sinusoidal waveform.
5. Device according to Claim 1 or 2, characterized in that the oneway current has a half-sinusoidal waveform.
6. Device according to Claim 1 or 2, characterized in that the oneway current has a triangular or sawtooth waveform.
7. Device according to Claim 1 or 2, characterized in that the one- way current has a square waveform.
8. Device according to one or more of the foregoing Claims, characterized in that the modulator has a waveform selected from the group comprising: a triangular waveform, a rectified sinusoidal waveform, a half- sinusoidal waveform or combinations thereof.
9. Device according to one or more of the foregoing Claims, characterized in that the one-way current has a frequency of between 100 and 3000 Hz.
10. Device according to one or more of the foregoing Claims, characterized in that the modulator has a frequency between 0J and 5 Hz and preferably between 0.5 and 1 Hz.
11. Device according to one or more of the foregoing Claims, characterized in that the current applied between the electrodes has a maximum value of 100 mA.
12. Method of administering an active compound by transdermal means, comprising the stages of:
• applying two electrodes, one of which is associated with a vehicle containing the active compound,
• generating a one-way current between the two said electrodes which is modulated in amplitude by a modulating signal of a periodic nature.
13. Method according to Claim 12, characterized in that said oneway current has a waveform selected from the group comprising: a rectified sinusoidal wave, a half-sinusoidal wave, a sawtooth wave, a triangular wave, a square wave, a positive sinusoidal wave, a train of pulses.
14. Method according to Claims 12 or 13, characterized in that said modulator has a waveform selected from the group comprising: a triangular waveform, a sawtooth waveform, a rectified sinusoidal waveform, a half- sinusoidal waveform or combinations thereof.
15. Method according to Claims 12, 13 or 14, characterized in that said modulating signal has an amplitude which can be varied between zero and a maximum value.
16. Method according to one or more of Claims 12 to 15, characterized in that said one-way current has a frequency of between 100 and 3000 Hz.
17. Method according to one or more of Claims 12 to 16, characterized in that said modulating signal has a frequency of between 0J and 5 Hz and preferably between 0.5 and 1 Hz.
18. Method according to one or more of the foregoing Claims, characterized in that the current between said electrodes varies between zero and a maximum value equal to 100 mA.
PCT/IT2000/000227 1999-06-09 2000-06-05 Ionophoretic drug delivery device WO2000074774A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
KR1020017015852A KR20020006547A (en) 1999-06-09 2000-06-05 Ionophoretic drug delivery device
DK00940738T DK1185334T3 (en) 1999-06-09 2000-06-05 Device and method for transdermal molecular transport
AT00940738T ATE279957T1 (en) 1999-06-09 2000-06-05 DEVICE FOR TRANSPORTING MOLECULES THROUGH THE SKIN
EP00940738A EP1185334B1 (en) 1999-06-09 2000-06-05 Device for transdermal molecular transport
JP2001501305A JP2003501166A (en) 1999-06-09 2000-06-05 Ion-permeable drug delivery device
CA002376251A CA2376251A1 (en) 1999-06-09 2000-06-05 Ionophoretic drug delivery device
BR0011459-6A BR0011459A (en) 1999-06-09 2000-06-05 Ionophoretic drug delivery device
AU55636/00A AU773339B2 (en) 1999-06-09 2000-06-05 Ionophoretic drug delivery device
DE60015125T DE60015125T2 (en) 1999-06-09 2000-06-05 DEVICE FOR TRANSPORTING MOLECULES THROUGH THE SKIN

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT1999FI000141A IT1315207B1 (en) 1999-06-09 1999-06-09 DEVICE AND METHOD FOR TRANSDERMIC MOLECULAR TRANSPORT.
ITFI99A000141 1999-06-09

Publications (1)

Publication Number Publication Date
WO2000074774A1 true WO2000074774A1 (en) 2000-12-14

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EP (1) EP1185334B1 (en)
JP (1) JP2003501166A (en)
KR (1) KR20020006547A (en)
AT (1) ATE279957T1 (en)
AU (1) AU773339B2 (en)
BR (1) BR0011459A (en)
CA (1) CA2376251A1 (en)
DE (1) DE60015125T2 (en)
DK (1) DK1185334T3 (en)
ES (1) ES2230115T3 (en)
IT (1) IT1315207B1 (en)
PT (1) PT1185334E (en)
RU (1) RU2271230C2 (en)
WO (1) WO2000074774A1 (en)

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WO2005035051A1 (en) * 2003-10-10 2005-04-21 Indiba Japan Co., Ltd. Portable ion introduction unit and method for dosing medicine
ITTO20120531A1 (en) * 2012-06-19 2013-12-20 Bruno Massimo Cetroni DEVICE FOR TRANSDERMIC AND / OR INTRADERMAL VEHICLE
WO2013190489A1 (en) * 2012-06-19 2013-12-27 Cetroni Bruno Massimo Device for transdermal and/or intradermal transport
EP3824947A1 (en) 2017-02-09 2021-05-26 Cetroni, Bruno Massimo Device for intracellular transport in resonance

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JP5963412B2 (en) * 2011-09-14 2016-08-03 日立マクセル株式会社 Beauty equipment
ITTO20120532A1 (en) * 2012-06-19 2013-12-20 Bruno Massimo Cetroni DEVICE FOR TRANSDERMIC AND / OR INTRADERMAL VEHICLE

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WO2005035051A1 (en) * 2003-10-10 2005-04-21 Indiba Japan Co., Ltd. Portable ion introduction unit and method for dosing medicine
ITTO20120531A1 (en) * 2012-06-19 2013-12-20 Bruno Massimo Cetroni DEVICE FOR TRANSDERMIC AND / OR INTRADERMAL VEHICLE
WO2013190489A1 (en) * 2012-06-19 2013-12-27 Cetroni Bruno Massimo Device for transdermal and/or intradermal transport
EP3824947A1 (en) 2017-02-09 2021-05-26 Cetroni, Bruno Massimo Device for intracellular transport in resonance

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EP1185334A1 (en) 2002-03-13
AU5563600A (en) 2000-12-28
ATE279957T1 (en) 2004-11-15
BR0011459A (en) 2002-04-23
IT1315207B1 (en) 2003-02-03
DK1185334T3 (en) 2004-12-06
DE60015125D1 (en) 2004-11-25
JP2003501166A (en) 2003-01-14
KR20020006547A (en) 2002-01-19
AU773339B2 (en) 2004-05-20
RU2271230C2 (en) 2006-03-10
DE60015125T2 (en) 2005-11-03
ITFI990141A1 (en) 2000-12-09
CA2376251A1 (en) 2000-12-14
PT1185334E (en) 2005-03-31
ES2230115T3 (en) 2005-05-01
EP1185334B1 (en) 2004-10-20

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